Cell Type and Nuclear Size Dependence of the Nuclear Deformation of Cells on a Micropillar Array

Abstract

While various cellular responses to materials have been published, little concerns the deformation of cell nuclei. Herein we fabricated a polymeric micropillar array of appropriate dimensions to trigger the significant self-deformation of cell nuclei and examined six cell types, which could be classified into cancerous cells (Hela and HepG2) versus healthy cells (HCvEpC, MC3T3-E1, NIH3T3, and hMSC) or epithelial-like cells (Hela, HepG2, and HCvEpC) versus fibroblast-like cells (MC3T3-E1, NIH3T3, and hMSC). While all of the cell types exhibited severe nuclear deformation on the poly(lactide- co-glycolide) (PLGA) micropillar array, the difference between the epithelial-like and fibroblast-like cells was much more significant than that between the cancerous and healthy cells. We also examined the statistics of nuclear shape indexes of cells with an inevitable dispersity of nuclear sizes. It was found that larger nuclei favored more significant deformation on the micropillar array for each cell type. In the same region of nuclear size, the parts of the epithelial-like cells exhibited more significant nuclear deformation than those of the fibroblast-like cells. Hence, this article reports the nuclear size dependence of the self-deformation of cell nuclei on micropillar arrays for the first time and meanwhile strengthens the cell-type dependence.

Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

“…This type of topography found numerous applications in cell function regulation and in the characterization of nuclear deformability. By changing pattern dimension, indeed, these structures could induce very peculiar and cell-dependent nuclear shaping, allowing, among others, the discrimination between normal and cancer cells (Davidson et al, 2009;Badique et al, 2013;Liu et al, 2019). Micropillar topographies, through nuclear deformation, could also influence differentiation pathways as shown by Liu et al (2016), who demonstrated a correlation between pillar height and spacing and the triggering of specific differentiation (i.e., osteogenesis or adipogenesis).…”

A Cell Culture Chip with Transparent, Micropillar-Decorated Bottom for Live Cell Imaging and Screening of Breast Cancer Cells

“…When Circularity on Ch-Patterned was compared with on Ch-Smooth, MDAMB231 cells showed significantly lower Circularity at the very beginning of the culture time, whereas MCF7 cells had Circularity that decreased over time. Nuclear deformation has been reported as a continuous process (can be observed even after the cell division as long as the cells are on the same topography) [50,74] and increases over time [52,53].…”

“…Previously, square pillar patterned substrates similar to those used in this study were used to characterize and measure cancer cell responses by our group and others [37,[50][51][52][53][54]. This type of square pillars were shown to induce the deformation of nuclei, especially in cancer cells.…”

Automated Cell Mechanical Characterization by On-Chip Sequential Squeezing: From Static to Dynamic

“…In most cases, variations among cells from the same cell line and inherent errors in measuring static mechanical properties exist side by side. Recently, analysis of the influence of mechanical properties on cancer cell migration indicates that cell recognition based on cell dynamic behavior analysis will not be influenced by the differences among cells caused by environmental disturbance or cell size variation. , However, such dynamic mechanical characterization in their research works required time-lapse observations for a long period, which limits the clinical diagnostic value . Inspired by the abovementioned research works, we tried to develop an efficient approach to excite dynamic cell behaviors and find the features valuable for cell recognition.…”